Flavored e-cigarette use in adolescents: Behavioral, cellular, and epigenetic mechanisms

青少年使用调味电子烟：行为、细胞和表观遗传机制

基本信息

批准号：
9521691
负责人：
Mariella De Biasi
金额：
$ 44.16万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-04-01 至 2022-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9521691
关键词：
Acute Address Adolescence Adolescent Adult Affect Age Aldehydes Area Behavioral Beverages Biochemical Brain Candy Centers for Disease Control and Prevention (U.S.)Cessation of life ChIP-seq Chemical Actions Chemicals Cigarette Clinical Research Complement Complex Consumption Cues Dependence Development Devices Disease Dopamine Dopaminergic Cell Dose Electronic cigarette Electrophysiology (science)Epigenetic Process Ethanol Exclusion Experimental Models Exposure to Familiarity Food Fostering Fruit Genes Goals High School Student Histones Human Inhalation Injections Investigation Lead Life Liquid substance Mass Spectrum Analysis Measures Menthol Modeling Modification Molecular Monitor Mus Neurons Nicotine Nicotine Dependence Oral Pathway interactions Periodicity Pharmaceutical Preparations Pharmacologic Actions Post-Translational Protein Processing Predisposition Property Rewards Risk Self Administration Sensory Series Stimulus Sucrose System Techniques Teenagers Testing Tobacco Weather addiction awake behavioral study dopaminergic neuron electronic cigarette use experience experimental study genetic approach histone modification in vivo interest junior high school neuroadaptation nicotine abuse nicotine exposure nicotine seeking behavior nicotine use nicotine vapor pre-clinical preclinical study preference response reward circuitry sensory input soft drink transcriptome vaping vapor young adult

项目摘要

E-cigarettes are increasingly used by teenagers, who are particularly vulnerable to the addictive properties of nicotine. With the exclusion of menthol, the use of flavor additives has been banned from traditional cigarettes, while e-cigarettes are marketed in over 7,000 different flavors. Many of those flavors are found in candy and popular soft drinks and, because they are familiar, make e-cigarettes more appealing to adolescents. We hypothesize that flavorants enhance nicotine reward through sensory and/or natural reward mechanisms. As a consequence, flavored e-cigarettes may promote nicotine experimentation, dependence, and eventually, the use of regular cigarettes. Understanding how flavors influence e-cigarette use is important for the implementation of regulatory rules that can reduce potential disease and death deriving from the consumption of this increasingly popular tobacco product. The goal of this application is to compare the rewarding and reinforcing properties of flavored vs. non-flavored e-cigarettes in adolescent mice. Our hypothesis is that flavored e-cigarettes are more rewarding than non-flavored e-cigarettes, and that flavor additives promote and sustain nicotine seeking in adolescents. The first goal is to determine whether sweet flavorants enhance adolescent nicotine reward and promote nicotine self-administration. The second goal is to investigate the possibility that a learned flavor preference, which models exposure to sweetened food and beverages at a young age, will further enhance flavor-induced nicotine reward and self-administration. Finally, we will determine whether exposure to flavored e-cigarettes at young age increases the risk of nicotine abuse in adulthood. These behavioral experiments will be complemented by a series of molecular investigations. First, we will employ in vivo tetrode recording to measure changes in dopamine neuron firing during exposure to flavored and non-flavored e-cig nicotine vapor. Second, we will utilize in vivo voltammetry techniques to quantitatively measure dopamine release in the NAc in response to inhalation of flavored vs.unflavored e-cigarette vapors. Third, we will utilize state-of-the art approaches to determine whether e-cigarette nicotine vapor changes the epigenetic landscape of reward- associated brain areas, and weather fruit flavorants have additive or synergistic effects.

青少年越来越容易受到上瘾的影响，越来越多地使用电子烟尼古丁的特性。由于薄荷醇的排除，已禁止使用风味添加剂传统香烟，而电子烟则以7,000多种不同的口味销售。其中许多口味可在糖果和受欢迎的软饮料中找到，并且由于熟悉，因此制作电子烟对青少年更具吸引力。我们假设味道通过感觉和/或自然奖励机制。结果，调味的电子烟可能会促进尼古丁实验，依赖性以及最终使用常规香烟。理解风味如何影响电子烟的使用对于实施监管规则很重要减少潜在的疾病和死亡，从而消耗这种越来越受欢迎的烟草产品。该应用的目的是比较调味的奖励和增强特性与青少年小鼠中的非味电子烟。我们的假设是调味的电子烟更多比非味的电子烟相比获得奖励，而这种风味添加剂可以促进和维持尼古丁寻找青少年。第一个目标是确定甜味剂是否增强了青少年尼古丁奖励并促进尼古丁自我管理。第二个目标是调查模型接触甜食和饮料的博学风味偏好的可能性在很小的时候，将进一步增强风味引起的尼古丁奖励和自我管理。最后，我们将确定在年轻时接触到调味的电子烟是否会增加尼古丁的风险成年后的虐待。这些行为实验将由一系列分子补充调查。首先，我们将使用体内四极管记录来测量多巴胺神经元的变化暴露于调味和非味的电子烟尼古丁蒸气时发射。第二，我们将在体内使用伏安技术以定量测量NAC中的多巴胺释放，以响应于吸入调味剂与未闻名的电子烟蒸气。第三，我们将利用最先进的方法确定电子烟尼古丁蒸气是否改变了奖励的表观遗传景观 - 相关的大脑区域和天气水果味剂具有累加或协同作用。